Sodium hydride → 6-Chloro-5-fluoro-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-pyrrolo[2,3-b:5,4-c']dipyridine

Participants

Reaction Steps

A suspension of 6-chloro-5-fluoro-9H-dipyrido[2,3-b;4′3′-d]pyrrole (9 g, 40.6 mmol) in DMF (90 mL) was placed in a cold water bath and treated portionwise with sodium hydride (60% suspension in mineral oil) (1.94 g, 48.5 mmol) keeping the internal temperature at 20-25° C. When gas evolution ceased (ca. 1 hour) the mixture was treated dropwise with 2-(trimethylsilyl)ethoxymethyl chloride (8.1 g, 8.7 mL, 48.5 mmol) keeping the internal temperature at 25-30° C. After stirring for a further 1 hour the mixture was partitioned between ethyl acetate and ice-cold 1N hydrochloric acid. The aqueous phase was further extracted with ethyl acetate and the combined organic phase was washed with water, aqueous potassium carbonate solution, water, and brine, dried (Na2SO4), filtered and evaporated in-vacuo. The residue was triturated with pentane:diethyl ether (ca. 20:1) to afford the title compound as a beige solid (11.4 g, 80%). The trituration liquors were evaporated and purified by chromatography to afford a second crop of title compound (0.85 g, 6%). Total yield=12.3 g, 86%. 1H NMR (400 MHz, CDCl3): 8.68-8.68 (m, 2H), 8.52 (dd, J=7.8, 1.7 Hz, 1H), 7.35 (dd, J=7.8, 4.8 Hz, 1H), 5.95 (s, 2H), 3.59 (t, J=8.2 Hz, 2H), 0.92 (t, J=8.2 Hz, 2H), −0.09 (d, J=0.5 Hz, 9H).

Provenance & Evidence